Interferon- γ Inhibits Transgene Expression Driven by SV40 or CMV Promoters but Augments Expression Driven by the Mammalian MHC I Promoter

Abstract

The use of mammalian gene expression vectors has become increasingly important for transgenics and gene therapy as well as basic research. Essential for the success of these vectors in medical research applications is the proper choice of promoter linked to the gene of interest. Many mammalian expression vectors use promoter elements from pathogenic viruses, including simian virus 40 (SV40) and cytomegalovirus (CMV). Lymphokines produced by the immune response to proteins expressed by these vectors could inhibit further transcription initiation by viral promoters. Our objective was to determine the effect of interferon-γ(IFN-γ) on transgene expression driven by a viral SV40 or CMV promoter/enhancer and the mammalian promoter/enhancer for the major histocompatibility complex class I (MHC I) gene. We transfected the luciferase gene driven by these three promoters into 14 cell lines of many tissues and several species. Luciferase assays of transfected cells untreated or treated with IFN-γ indicated that, although the viral promoters could drive luciferase production in all cell lines tested to greater or lesser levels than the MHC I promoter, treatment with IFN-γ caused inhibition of transgene expression in most of the cell lines and amplification of the MHC I promoter-driven transgene expression in all cell lines. These data indicate that the SV40 and CMV promoter/enhancers may not be a suitable choice for gene delivery especially for immune response applications or in patients where IFN levels may be elevated. The MHC I promoter/enhancer, on the other hand, may be an ideal transgene promoter for applications involving the immune system.

Overview summary

Interferon-γ (IFN-γ) treatment of transiently or stably transfected cell lines of various tissues and species resulted in suppression of luciferase transgene expression driven by the SV40 or CMV viral promoters. However, luciferase transgene expression driven by the mammalian MHC I promoter was enhanced. These results offer an explanation for the short-lived transgene expression observed by many researchers using viral promoters to express transgenes. Our data suggest that for long-term sustained transgene expression necessary for an optimal immune response, the mammalian MHC I promoter/enhancer could be a better choice than the commonly used viral promoters.